Management of Brain Metastases

Management of Brain Metastases

The article by Wen and Loeffler provides a comprehensive, timely,
well-written review of the management of cerebral metastases. Both
older studies and more recent reports on advances in the surgical,
radiotherapeutic, and chemotherapeutic approaches to the treatment of
cerebral metastases are covered. Consensus pathways are proposed for
the management of patients with cerebral metastases.

Cerebral metastases are an increasingly common problem in the
management of cancer patients, for several reasons.[1-3] Better
chemotherapeutic agents, radiation, and surgical interventions are
achieving good control of systemic cancer.[4] Cerebral metastases are
seen as the primary site of disease treatment failure or as a
manifestation of poorly controlled disease.[4] The use of head
computed tomography (CT) and magnetic resonance imaging (MRI) has
also increased the recognition of this problem; many of these
metastases were not detected in the past, specifically since
postmortem examinations were not performed routinely.[3,5]

External-Beam Radiation Therapy

There is consensus that external-beam radiation is effective in
controlling cerebral metastases.[6] Wen and Loeffler elegantly review
published studies of this treatment modality. Variations in total
radiation doses and fractionation schemes, the inclusion of different
types of tumors, and the status of the primary disease site make it
difficult to compare many of these studies.[4,7] Studies that include
more radioresistant primaries, for example, cannot be compared to
trials that include radiosensitive tumors.[4,7,8]

One obvious message of this review is that future studies should be
prospective and randomized, and should compare patients of similar
age and functional status with similar tumor histology, number of
cerebral metastases, and status of the primary disease.[9] All of
these factors can be important prognostic indicators, regardless of
the radiation dose or fractionation scheme used.

Conventional Surgery, Stereotactic Radiosurgery, and Chemotherapy

Recently introduced diagnostic tools, such as CT/MRI scanning, have
made it possible to attempt early surgical resection of a single,
isolated cerebral metastasis.[10-12] This intervention has resulted
in longer life expectancy.[12]

The addition of postoperative radiation therapy has led to less local
disease recurrence and has improved patients quality of
life.[13,14] It has not, however, improved survival.[14] Again, it is
difficult to compare studies because many include a heterogeneous mix
of tumors, with their varied degree of responsiveness to
radiation.[12-14] Definitive answers to questions about the role of
radiation following tumor resection will also require prospective,
randomized trials that include patients of comparable age and
functional status who have similar tumor histology and status of
systemic disease.

Stereotactic radiosurgery is a powerful tool for treating cerebral
metastases. It can take the form of a high-energy x-ray produced by
linear accelerators, gamma-radiation delivered via the gamma knife,
or heavy-particle proton-beam radiation.[15-17]

The roles of radiosurgery in treating cerebral metastases in
difficult-to-reach areas, as well as resectable areas, are currently
being defined.[17] Early indicators suggest that radiosurgery may be
a cost-effective way of treating cerebral metastases.[18] Adequate,
prospective, randomized clinical trials (as described earlier)
comparing stereotactic radiosurgery to surgical intervention are
needed. At present, radiosurgery is a good option for patients with
metastases in hard-to-reach areas or those with small metastases from
radioresistant primaries, such as melanoma.

The role of chemotherapy in the treatment of cerebral metastases is
limited to chemosensitive tumors, such as small-cell carcinoma of the
lung, choriocarcinoma, or germ cell tumors.[19] Many cerebral
metastases, such as those from non-small-cell lung cancer and
melanoma, are not chemosensitive and will not respond to chemotherapy.[19]

Leptomeningeal Metastases With Parenchymal Metastases

One area that this review does not address is the management of
concomitant leptomeningeal metastases with parenchymal metastases.
This is important for certain types of metastases, such as those from
small-cell carcinoma of the lung, systemic lymphoma, or
germinoma.[20] Staging with cerebrospinal fluid cytology and MRI
scanning of the spinal cord are legitimate concerns in managing these tumors.[20]

Summary

Overall, this review is comprehensive, informative, and timely. It
certainly raises issues about the integration of external-beam
radiation, conventional surgery, and radiosurgery into the treatment
of cerebral metastases. The article also emphasizes the need for more
prospective, randomized trials to define the effectiveness of these
treatments. Finally, it stresses that stratification of patients
according to age, functional status, status of the primary disease,
and tumor histology is crucial to making these clinical studies more comparable.